The art of tablet making involves the making of a composition containing an active ingredient which is sturdy for packaging and handling, and disintegrable in a predictable manner.
Fast-dissolving and fast-disintegrating tablets are especially important in the field of orally ingested drugs. Many people are unwilling and/or unable to swallow tablets, capsules or other traditional solid dosage forms. This is especially the case of pharmaceuticals for paediatric or geriatric use.
One approach suitable for these persons is the use of effervescent tablets or granules. However, the use of effervescent tablets requires preparatory steps before administration of the drug and the presence of water and a suitable mixing container. In addition, the manufacture and stability of effervescent tablets is often problematic. Another possibility is the use of a chewing gum or chewing tablet containing a drug capable of absorption through the buccal cavity (U.S. Pat. No. 5,225,197). Substantial disadvantages inherent in such a delivery system are that many active drug ingredients are not suitable for buccal absorption and that many persons are not able to chew gums or tablets because of braces, dental work, and the like. Furthermore, gums are often difficult to prepare.
Two main technologies are presently used to obtain pharmaceutical dosage forms for fast disintegration on contact with saliva in the buccal cavity. These methods are summarized in M. Sugimoto, K. Matsubara, Y. Koida und M. Kobayashi, Pharm. Dev. Technol. 6 (4), 487-493 (2001):
(1) The active ingredient is mixed with water-soluble diluents and compressed on a tableting machine at low to medium compression force. This is the more conventional approach, and very often does not give tablets with the required tensile strength and reasonable disintegration time. A more recent approach is the OraSolv™ technology, which involves incorporating microencapsulated drug ingredients into a tablet obtained by compression (U.S. Pat. No. 5,178,878). The tablets have to be packed into special peel-off blister packs because their mechanical resistance is insufficient in normal blister packs. Rapidly dissolving tablets have been produced using suitable crystalline sugar structures under adapted curing conditions (U.S. Pat. No. 5,866,163). Further compressed, rapidly dissolvable dosage forms including an active ingredient and a matrix composed of a nondirect compression filler and a lubricant are disclosed in U.S. Pat. No. 6,221,392.
(2) A suspension is prepared with the active ingredient and appropriate excipients. The suspension is dispensed into blister packs and freeze-dried (U.S. Pat. No. 4,371,516). This approach usually gives tablets with porous structure, reasonable tensile strength and disintegration time, but is time-consuming and requires a costly freeze drying process. A corresponding process marketed under the term Zydis® Technology is protected by U.S. Pat. No. 4,642,903 and EP 295 242. Particular forms of this technology are protected e.g. in U.S. Pat. Nos. 5,976,577; 6,156,359; 6,413,549; 6,423,342; 6,509,040; and 6,709.669.
The effectiveness of a freeze-drying process always depends on the physico-chemical parameters of the active substances used. Replacing the freeze-drying step by conventional drying at room temperature or elevated temperature, also drying with microwave radiation, is disclosed in International Patent Application WO 97/38679, but is likewise time and energy-consuming, and is also limited to active substances which survive such conditions. A convenient procedure to overcome these drawbacks is described in European Patent Application EP03405901.4.